We are investigating metal-ion interactions with peptides to measure relative metal-ion affinities of calcium with peptides that contain sequence motifs that are known to bind calcium. The interactions of Fe(II) with small peptides containing cysteine and Na(I) with cyclic peptides illustrate a second motivation whereby we seek new structural methods for biomolecules. The simple expedient of introducing a metal-cationized peptide or cyclic peptides is a means for taking "another look" at how a molecule fragments and determining its structure. The research has been extended to the protein calmodulin. We are developing a method to demonstrate that electrospray and H/D exchange can be used to follow Ca(II)-induced folding changes followed by noncovalent finding of calmodulin with hydrophobic peptides. The results serve as an appropriate demonstration of this relatively new capability of MS.